Timur A A, Driscoll D J, Wang Q
Center for Molecular Genetics, ND40, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Cell Mol Life Sci. 2005 Jul;62(13):1434-47. doi: 10.1007/s00018-005-4523-7.
Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining 'increased angiogenesis' as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.
血管形态发生对于胚胎发育、正常生理状况（如伤口愈合）以及病理过程（如动脉粥样硬化、癌症）而言是一个至关重要的过程。对血管异常的遗传学研究已促使人们鉴定出参与血管形态发生的关键基因。针对克-特综合征（KTS）克隆出了一个易感基因VG5Q（正式命名为AGGF1）。AGGF1编码一种强效血管生成因子，且与KTS相关的突变增强了AGGF1的血管生成活性，将“血管生成增加”定义为KTS发病机制的一种分子机制。类似的研究已鉴定出其他参与血管异常的基因是血管形态发生的重要基因，包括TIE2、VEGFR-3、RASA1、KRIT1、MGC4607、PDCD10、球囊素、FOXC2、NEMO、SOX18、ENG、ACVRLK1、MADH4、NDP、TIMP3、Notch3、COL3A1和PTEN。未来对血管异常基因的研究将为血管形态发生的分子机制提供深入见解，并可能促使开发出治疗这些及其他血管生成相关疾病（包括冠状动脉疾病和癌症）的治疗策略。
